Qualification and Delivery of All Things Pharmaceutical. Blaik C Jensen Associate Quality Engineering Consultant

Transcription

1 Qualification and Delivery of All Things Pharmaceutical Blaik C Jensen Associate Quality Engineering Consultant

2 Commissioning and Qualification Sequence Design Follows the methodology found in the ISPE Baseline Pharmaceutical Engineering Guide, Volume 5, Commissioning and Qualification, First Edition, March 2001 Commissioning UR - GEP Design Review II, NI System Class. II Maintenance Program DI DI UR - QR Qualification

3 System Classification Elements: Listing of all systems to be delivered by the project Determination of Direct Impact (DI), Indirect Impact (II) or No Impact (NI) by answering battery of questions Justification of Indirect Impact and No Impact classifications Indication of commissioning and qualification activities that apply Project Impact: Gives structure to the commissioning and qualification (C&Q) effort System listing a useful tool for the project team

4 User Requirements Elements: Unique requirement number Acceptance Criteria Specific Measurable Achievable Realistic Traceable General Testing Philosophy Requirement Rationale Avoid restating the engineering specifications in the UR. Only include those attributes that the user truly wants and that need to be tested and verified in the C&Q protocols to prove compliance.

5 User Requirements Project impact: Provide clear separation between critical (product related) requirements that needed qualification and non-critical requirements that needed only commissioning Update qualification requirements based on results from testing and operating data obtained during commissioning However, changes to UR documents require sound engineering and data based rationale thereby controlling scope creep in both cost and activities

6 Review of vendor submittals against the URs to verify that the design meets all applicable requirements. Elements: Date of review Listing of Attendees System reviewed Design documents reviewed Traceability matrix detailing which URs were verified by which document Notes

7 Project impact: Perform Design Qualification on all Direct Impact systems, Enhanced Design Review on commissioned systems Document justification of design impact on or exceptions to URs Transfer panel hygienic piping level when slope was required Powder painted HEPA filter enclosures when carbon steel not permitted /Purchase Order not finalized until after completed, but could occur before approval Weakness in the vendor specifications as well as gaps in the vendor submittal documentation identified before system build begins, preventing equipment remediation in the field

8 Component Criticality Assessment Examination of all components in all Direct Impact (DI) and Indirect Impact (II) systems to determine how that component can affect product SIS. Elements: Listing of all system components with a P&ID tag number General listing of piping materials, hand valves, steam traps, etc. Answer a battery of questions

9 Component Criticality Assessment Project impact: Do after, but could be done at the same time Answer questions until a Yes is obtained, then stop answering questions OR answer all questions Perform on all II systems as a check on the initial system classification considered a living document, so establish its own revision control Changes to the system will require revisiting the

10 Elements: determination of Critical or Non-critical Conduct Reliability Centered Maintenance review on all systems FMEA results affect PM frequency and necessity Electronic loading of data into CMMS Ensure engineers have necessary experience to adequately evaluate the recommended maintenance actions and intervals Example: Initially no periodic check of mechanical seals on hygienic pumps

11 Factory Acceptance Testing Elements: Test all equipment functions at manufacturer s facility Testing document provided by manufacturer or developed by project Check dimensional tolerances of connection points (skidded equipment) List equipment deficiencies, needed corrections and repairs Representatives from engineering, automation, project admin present (and quality assurance if desired)

12 Factory Acceptance Testing Project impact: only done on a portion of the systems, mainly packaged systems Corrections done at factory before shipment more cost effective Materials, tooling, technicians are already present Vendor motivated to ship so work done quickly Project loses leverage once the equipment ships (FOB), so wait until the equipment is right Do not allow shipment until all critical corrections are completed and all required documents are delivered!!!

13 Receipt Verification Installation Verification Elements: Equipment attributes printed out from data Manufacturer Model Number Material of construction Range of operation Etc. Verification of attributes by field inspection or document check Field check of equipment and instrument installation (flow valves) Walk down of the Piping and Instrumentation Diagram (P&ID) Approval by project engineer not involved in attribute verification No approval by QA needed Perform at point of receipt by project team or third party

14 System Startup Protocol Controlled approach to starting up equipment so that both the equipment and the operators are protected Elements: System Startup Checklist () Check supporting utilities (electric, chilled water, steam, etc.) Check equipment conditions (pumps aligned, lubrication, guards in place, proper rotation, etc.) No QA approval needed

15 Site Acceptance Testing Testing performed at the construction site to evaluate equipment operation and function with site utilities and support. Elements: Testing at installation site with the site utilities May be same test performed during Manufacturer representative on site to address problems Great opportunity for operator training and familiarization

16 Functional Testing Elements: Acceptance Criteria copied from the GEP User Requirements Test Cases copied from the Operational Qualification protocol Any other tests as desired by the process and equipment engineers Project impact: Excellent opportunity to kick the tires Fully test the system s operating procedures Protocols readily and easily changed by engineers Test failures occurred and were corrected expeditiously so tests go smoothly Approval by QA not needed

17 Functional Testing Examples: Sprayball testing conducted under with the several necessary iterations controlled by engineering CIP testing conducted during was completed flawlessly Improperly piped CIP/CSTM supply to a bioreactor missed during was identified (when steam appeared where it was not expected) and corrected with no impact to overall facility delivery schedule HVAC testing identified undersized exhaust fans, supply fans with vibration problems and incorrect ducting design leading to flow stratification, all problems were corrected before EM (vendor bore cost of remediation)

18 Qualification Documented evidence that the equipment or systems are suitable for the intended purpose and perform as intended using Installation Qualification (), Operational Qualification () and Performance Qualification () protocols Common elements: Clear statements concerning protocol execution Acceptance Criteria copied from the Quality Related User Requirements Second person verification by project personnel not involved in verifying fulfillment of acceptance criteria Pre-approval by technical personnel and QA

19 Qualification Project impact: Signature log not only captured all protocol executors and reviewers but required certification that training was completed Specific second person verification of training discovered many training gaps before they became compliance issues Final Qualification Summary Report served as approval for both and Added prerequisite to protocol to verify completion Only Direct Impact utilities and some critical systems had a protocol

20 Other Success Factors: Co-location of Resources Commissioning and Qualification (C&Q) and QA resources located in the same area during initial project phases become an integrated team Close proximity promots informal discussions, consultation opportunities, and timely quality direction Result: Promoted a good working relationship between project personnel and the quality unit. Late in project execution, project personnel have sought out quality unit personnel to report project difficulties and testing failures to ask for direction, even after the team was split up.

21 Other Success Factors: Key Execution Factors Project roles are well defined across all involved areas Strong sense of ownership and responsibility amongst all defined roles Assigned project personnel act as integrated team members, but able to take leadership roles when necessary Though QA neither reviews nor approves any commissioning documents, QA does have oversight by reviewing the commissioning scope and approving the Commissioning Master Plan and system receipt verification and installation verification form templates QA also provides commissioning oversight by auditing selected commissioning documents and other records, especially those leveraged by Qualification

22 Other Success Factors: Early Quality Assurance Involvement Quality Expectations and Needs document QA Engineer on Design Team from project kick-off for initial design and User Requirement (UR) input Continuous QA presence on project team for timely approval of strategy and solutions and/or consultation at key decision points QA attend on critical systems and equipment Audits and spot checks of commissioning documents leading to identification and timely resolution of possible GMP issues, especially for documents to be leveraged for and QA Rep with engineering expertise is vital Success: Many design flaws identified and corrected in Design Qualification

23 Project Final Results Project costs controllable by minimizing changes and scope creep. Quality QA presence from project inception controls quality of final outcome. Cost Schedule Project delivery controlled by minimizing scope creep.

24 Examples Capital Projects B360 Clinical Trial Pilot Plant IE42 Biopharmaceutical Manufacturing Facility Purchasing of Lab Equipment Bread

25 Research and Development Clinical Trial Pilot Plant Schedule GMP operations began 02 Oct 2006, as scheduled Budget 7% more than the budget target Quality Final audit by Lilly Corporate Quality Assurance had no observations or findings.

26 Biopharmaceutical Manufacturing Facility Schedule Facility was delivered 02 Nov 2010, as scheduled Budget Did not exceed the budget target Quality Facility has been certified by regulatory authority to manufacture Drug Substances

27 Purchasing of Lab Equipment Lilly uses a System Qualification (SQ) protocol to gather up all the elements of Commissioning and Qualification into a package of less than 40 pages. Preapproval signatures also approve the User Requirements and Design Qualification portions of the SQ protocol and usually skipped as lab equipment is usually COTS type procurement and documents are attached if not part of the protocol usually skipped as executors go right into, which is fine as the testing is well defined by the lab methods

28 Bread Call from home, Pick up some bread User Requirement At the store, look at Nutritional Information Design Qualification Show bread to spouse/significant other Installation Verification / Installation Qualification Make some toast or a sandwich Operational Qualification / Process Validation

29 Summary The commissioning process includes design, receipt, installation and functional verification, performed by the construction and process engineers, using standard operating procedures that are reviewed and approved by QA. This approach allows for identification of potentially delaying defects in system fabrication, installation and performance before qualification begins, allowing time for remediation without impacting the project timeline. The keystone is User Requirements.

30 Credits Thanks for: Project Information Bruce McDonald Lilly GFD Project Manager Michael Dunne Jacobs C&Q Manager Bill Allen Jacobs C&Q Assistant Manager Contributions to this presentation Kent Kyburz Lilly BR&D Manufacturing Team Leader

31 Questions